ACTH(4–10) comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Updated 2026-08-01. Numbers and descriptions here follow the published literature rather than marketing material.
从分子层面看，Semax 是线性七肽，没有二硫键、糖基或脂链修饰，N 端为游离氨基，C 端为游离羧基。分子含组氨酸与谷氨酸侧链，因此在水和甲醇等极性溶剂中溶解良好，在非极性溶剂中溶解有限。计算分子量约为 814 Da，与其质子化离子的质荷比吻合，可用于质谱确认。
稳定性主要由水解与氧化两条路径支配。肽键在中性或弱酸性条件下相对稳定，遇到强碱或长时间高温则明显断裂；甲硫氨酸侧链容易被氧化成亚砜，使主峰前移并拉低实际含量。金属离子、光照和反复冻融会进一步促进降解或聚集。冻干粉在低温避光条件下可存放较长时间，配制后的水溶液通常需要冷藏并尽快用完。
纯度评估以反相高效液相色谱为主，通过主峰面积百分比给出粗略结果，再配合电喷雾质谱核对分子量。氨基酸分析可验证组成比例，手性色谱或毛细管电泳用于检查残基构型。常见杂质包括缺失序列的短肽、氧化产物与二聚体。由于多数市售品不附带完整检验报告，独立第三方检测常被用来核实标称值。
The compound was developed in the 1980s at the Institute of Molecular Genetics in Moscow, where it emerged from research on short ACTH fragments and their effects on the central nervous system. Russian pharmaceutical listings describe it as a nootropic and neuroprotective agent, most often formulated as nasal drops. It is not a marketed medicine in the United States or the European Union, and no pharmacopoeial monograph covers it. Consequently, most published clinical experience with the substance originates from a small number of research centres, mainly in Russia and neighbouring countries.
Pharmacological accounts link semax to melanocortin signalling and to modulation of neurotrophic factor expression, particularly brain-derived neurotrophic factor and nerve growth factor. Much of this evidence comes from rodent studies using intranasal delivery, a route chosen because it allows peptides to reach the central nervous system with limited systemic exposure. Whether the same mechanisms operate in humans at comparable magnitude remains an open question. The precise receptor or receptors responsible for the reported behavioural and neuroprotective effects have not been conclusively identified.
Clinical reports describe use in ischaemic stroke, transient ischaemic attack, optic nerve conditions, and cognitive complaints, but most of these studies are small and were conducted in a single region. Systematic reviews have generally described the evidence base as limited in size and variable in methodological quality. Randomised controlled data suitable for international regulatory assessment are scarce. As a result, major treatment guidelines outside Russia do not include the peptide, and interest in it remains largely research-driven rather than routine clinical.
| Property | Value | Notes |
|---|---|---|
| 分子式 | C37H51N9O10S | 游离碱形式 |
| 等电点 | 约 6.5 | 估算值，随缓冲体系变化 |
| 主要降解途径 | 水解与氧化 | 侧链氧化最为常见 |
| 溶液储存 | 2 至 8 摄氏度避光 | 避免反复冻融 |
| 常规分析手段 | 反相色谱与质谱联用 | 氨基酸分析辅助核对 |
Proposed mechanisms center on neurotrophic signaling rather than on classical melanocortin receptor activation. Rodent experiments have reported shifts in the expression of brain-derived neurotrophic factor and nerve growth factor after administration, together with changes in the associated receptor systems. Several authors argue that the peptide acts largely through its degradation products and their interaction with peptidergic pathways, but this remains a hypothesis rather than a settled finding. No single molecular target has been identified in a way that the field broadly accepts.
Published research covers ischemic stroke, traumatic brain injury, cognitive impairment, optic nerve conditions and attention-related measures. Much of the human evidence comes from small trials conducted in one country, which limits how far the results generalize. Animal models supply the larger share of the data, and effects seen in rodents do not transfer automatically to people. Reviews have noted that methodological reporting is often incomplete, making it difficult to pool results or compare treatment schedules across studies.
Pharmacokinetic accounts emphasize rapid breakdown. After intravenous dosing the intact peptide disappears from blood within minutes, and nasal delivery produces low but measurable concentrations. Metabolites rather than the parent molecule may account for part of the observed activity, although the relative contribution is unresolved. Dosing in the literature varies widely and no optimal schedule has been agreed. These gaps are regularly cited as a reason the findings have not produced broad clinical adoption beyond the original research setting.
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. Its design combines the ACTH(4-7) core fragment with a C-terminal Pro-Gly-Pro extension, a modification intended to improve stability and prolong activity. The molecule is hydrophilic, carries no lipid chains or glycosylation, and has a theoretical mass just over 810 daltons in its free form. All seven residues are proteinogenic amino acids, so no non-natural building blocks appear in the backbone. A free N-terminal methionine and C-terminal proline define the unmodified parent peptide.
The compound was developed during the 1980s at the Institute of Molecular Genetics in Moscow as part of research on fragments of adrenocorticotropic hormone. Early work examined short ACTH-derived sequences that retained neurotrophic effects while lacking the endocrine activity of the full hormone. Semax entered clinical use in Russia during the 1990s, where it received registration for several neurological indications. Outside that region it remained primarily a laboratory research material rather than an approved therapeutic. English-language literature on it grew more slowly and frequently cited the original Russian studies.
Terminology around the compound varies by source. It appears in catalogues and papers as Semax, as the heptapeptide ACTH(4-7)-Pro-Gly-Pro, and under various alphanumeric laboratory codes used by individual suppliers. These names refer to the same sequence but may imply different salt forms, purity grades, or counter-ions. Peptide databases usually list the free base mass, while product descriptions sometimes report acetate or trifluoroacetate salts with a different formula weight. Because naming conventions for research peptides are not standardised across vendors, checking the declared sequence and measured mass is more reliable than relying on a trade name alone.
In general, a starting molecule is adhered to a solid support (typically an insoluble polymer), then additional reactions are performed, and the final product is purified and then cleaved from the solid support. Since the molecules of interest are attached to a solid support, it is possible to reduce the purification after each reaction to a single filtration/wash step, eliminating the need for tedious liquid-liquid extraction and solvent evaporation steps that most synthetic chemistry involves. Furthermore, by using heterogeneous reactants, excess reagents can be used to drive sluggish reactions to completion, which can further improve yields. Excess reagents can simply be washed away without the need for additional purification steps such as chromatography.
With its weight rested on the pelvis, it may have been free to move the hindlimbs. Getting back up again might have involved some stabilization from the diminutive forelimbs. The latter known as Newman's pushup theory has been debated. Nonetheless, Tyrannosaurus was probably able to get up if it fell, which only would have required placing the limbs below the center of gravity, with the tail as an effective counterbalance. Healed stress fractures in the forelimbs have been put forward both as evidence that the arms cannot have been very useful and as evidence that they were indeed used and acquired wounds, like the rest of the body.
Metal rods can be surgically inserted in the long bones to improve strength, a procedure developed by Harold A. Sofield when he was Chief of Staff at Chicago's Shriners Hospitals for Children, a hospital that offers orthopedic care and surgery to children regardless of their family's ability to pay. Large numbers of children with OI came to Shriners, and Sofield experimented with various methods to strengthen their bones. In 1959, with Edward A. Millar [sic], Sofield wrote a seminal article describing a three-part surgery that seemed radical at the time: precisely breaking the bones ("fragmentation"), putting the resulting bone fragments in a straight line ("realignment"), then placing metal rods into the intramedullary canals of the long bones to stabilize and strengthen them ("rod fixation"). His treatment proved useful for increasing the mobility of people with OI, and it has been adopted throughout the world—it became standard surgical treatment for severe OI by 1979, in which year David Sillence found that ≈2⁄3 of the patients he surveyed with OI type III had undergone at least one rodding surgery. Rodding surgery is often done with the hope that it will offer a path to ambulation, walking, to patients with moderate or severe OI.
=== Actin and myosin === Muscles contract and stretch via the steerable sliding/grasping of the myosin interacting with actin fibers. Actin consists of two polypeptides in a helix and myosin has a small heart-shaped structure, cross-bridge. The bind and unbind processes of cross-bridge attaching on actin filament help relative movement of these collagens and hence the whole muscle.
Sources: en.wikipedia.org
== Binding mechanism == Single-stranded CHPs bind to denatured collagen chains and gelatin in a manner that is unique from other targeting mechanisms, in that they specifically recognize a unique structural motif (collagen triple helix) for folding and chain assembly, as opposed to specific epitopes binding that is seen for monoclonal antibodies (mAbs), for example. Due to their unique targeting mechanism, CHPs have a high binding specificity towards denatured collagen chains but have almost no affinity for intact (triple helical) collagen. CHPs can broadly target collagen chains that have been denatured by thermal, chemical, mechanical, or enzymatic processes, as well as multiple collagen types (e.g., Col I, II, IV). Studies also showed CHPs and their fluorophore conjugates have superior stability in contact with serum.
Type I collagen production is inhibited by the inability of the altered procollagen strands to associate and form the triple-stranded, ropelike structure of mature collagen. These alterations negatively affect tissues that are rich in type I collagen, such as the skin, bones, teeth, and tendons, leading to the signs and symptoms of type III osteogenesis imperfecta. Osteogenesis imperfecta, type IV: Several different types of mutations in the COL1A1 gene cause osteogenesis imperfecta type IV. These mutations may involve missing pieces of the COL1A1 gene or changes in base pairs (the building blocks of DNA). These gene alterations result in a protein that is missing segments or has amino acid substitutions; specifically, the amino acid glycine is replaced by another amino acid. All of these changes interfere with the formation of the mature triple-stranded collagen molecule and prevent the production of mature type I collagen, which results in type IV osteogenesis imperfecta. Osteoporosis: Osteoporosis is a condition that makes bones progressively more brittle and prone to fracturing. A particular variation (polymorphism) in the COL1A1 gene appears to increase the risk of developing osteoporosis. A specific variation at Sp1 binding site is shown to be associated with increased risk of low bone mass and vertebral fracture, because of the changes the COL1A1 protein produced from one copy of the gene. Several studies have shown that women with this particular genetic variation at Sp1 site are more likely to have signs of osteoporosis than are women without the variation.
=== Radiometric dating === Two radiometric dating methods involve thorium isotopes: uranium–thorium dating, based on the decay of 234U to 230Th, and ionium–thorium dating, which measures the ratio of 232Th to 230Th. These rely on the fact that 232Th is a primordial radioisotope, but 230Th only occurs as an intermediate decay product in the decay chain of 238U. Uranium–thorium dating is a relatively short-range process because of the short half-lives of 234U and 230Th relative to the age of the Earth: it is also accompanied by a sister process involving the alpha decay of 235U into 231Th, which very quickly becomes the longer-lived 231Pa, and this process is often used to check the results of uranium–thorium dating. Uranium–thorium dating is commonly used to determine the age of calcium carbonate materials such as speleothem or coral, because uranium is more soluble in water than thorium and protactinium, which are selectively precipitated into ocean-floor sediments, where their ratios are measured. The scheme has a range of several hundred thousand years. Ionium–thorium dating is a related process, which exploits the insolubility of thorium (both 232Th and 230Th) and thus its presence in ocean sediments to date these sediments by measuring the ratio of 232Th to 230Th. Both of these dating methods assume that the proportion of 230Th to 232Th is a constant during the period when the sediment layer was formed, that the sediment did not already contain thorium before contributions from the decay of uranium, and that the thorium cannot migrate within the sediment layer.
Sources: en.wikipedia.org
电喷雾或基质辅助激光解吸电离质谱是常用手段，测得的质子化离子质荷比可换算为分子量。结果与理论值落在合理误差内，才支持结构一致的判断。
甲硫氨酸侧链含硫醚，在氧气、光照或金属离子存在时容易被氧化。氧化产物极性略增，常在色谱图上表现为主峰之前的肩峰或前伸峰。
通常建议冷藏避光，并在较短时间内使用。不存在适用于所有配方的统一期限，具体取决于浓度、缓冲体系与容器材质。
It is described as a synthetic analogue of the ACTH(4–10) fragment, a short segment of adrenocorticotropic hormone. Its sequence differs from that fragment and includes two proline residues, which influence stability and behaviour in solution.